title: Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy.
abstract: BACKGROUND
  We studied the relationships among Cx43, CD105, and VEGF in specimens of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with respect to recurrence and metastasis.
  
  
  METHODS
  Expressions of Cx43, CD105, and VEGF in 234 HCC tissue specimens were examined using tissue microarray and immunohistochemistry. Cx43 mRNA expression was examined in 38 frozen HCC specimens using RT-PCR. Correlations between these expressions and tumor recurrence, metastasis, and prognosis were analyzed using Kaplan-Meier and Cox regression analyses.
  
  
  RESULTS
  Cx43 expression correlated with early tumor recurrence (P = 0.001), disease-free survival (P = 0.026), and overall survival (P = 0.000) in patients with serum AFP < 400 ng/ml, but not in those with serum AFP ≥ 400 μg/L. Cx43 expression is an independent predictor of later recurrence and longer overall survival and is inversely correlated with expression of CD105 and VEGF (P = 0.018 and 0.023, respectively), histological differentiation (P = 0.002), vessel tumor embolism (P = 0.029), and focal number (P = 0.017). Immunohistochemistry showed that Cx43 expression in patients with low AFP was lower in patients with distant metastases than in those with no metastasis or those with liver metastasis. Patients with early recurrence expressed less Cx43 mRNA than did those with no recurrence (χ2 = 9.827, P = 0.002).
  
  
  CONCLUSIONS
  Cx43 expression can delay early HCC recurrence, metastasis, and poor prognosis after radical hepatectomy in patients with HBV-related HCC and low AFP.
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Hospital of Medical College Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Zu-Sen
authors.initials: ZS
authors.lastname: Wang
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Wu
authors.forename: Xin
authors.initials: X
authors.lastname: Yi
authors.forename: Chao
authors.initials: C
authors.lastname: Geng
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Li
authors.forename: Ru-Yong
authors.initials: RY
authors.lastname: Yao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018031:Connexin 43 / Q000032:analysis / Q000096:biosynthesis*; D018572:Disease-Free Survival; D000071063:Endoglin; D005260:Female; D006498:Hepatectomy; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000096:biosynthesis; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D018031:Connexin 43; C064206:ENG protein, human; D000071063:Endoglin; C500216:GJA1 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D000509:alpha-Fetoproteins